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Clinical Research

Tirzepatide outcompetes long-acting insulin in managing type 2 diabetes: a meta-analysis of three phase 3 randomized controlled trials

International Journal of Obesity volume 48, pages 1684–1695 (2024)Cite this article

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Abstract

In this systematic review and meta-analysis, we compared the efficacy and safety of tirzepatide with those of long-acting or ultra-long-acting insulin for type 2 diabetes. PubMed, Web of Science, Scopus, and Google Scholar were searched from the inception to August 20, 2023. All clinical trials or randomized clinical trials comparing the efficacy of tirzepatide with long-acting or ultra-long-acting insulin for treating type 2 diabetes were included. Three randomized clinical trials, namely SURPASS-3, SURPASS-4, and SURPASS-AP-Combo, with 4339 patients were included. Compared with daily insulin glargine and degludec, once-weekly tirzepatide significantly decreased HbA1c (WMD −1.08%, 95% CI (−1.37, −0.78)), 2h-posprandial blood sugar (BS) (WMD −28.19 mg/dL, 95% CI (−44.98, −11.41)), pre-meal BS (WMD −11.86 mg/dL, 95% CI (−22.83, −0.9)), body weight (WMD −10.61 kg, 95% CI (−13.24, −7.97)), systolic blood pressure (WMD −6.47 mmHg, 95% CI (−8.32, −4.61)), diastolic blood pressure (WMD −2.30 mmHg, 95% CI (−3.05, −1.55)), total cholesterol (WMD −4.78%, 95% CI (−7.05, −2.50)), triglyceride (WMD −14.49%, 95% CI (−19.55, −9.43)), LDL cholesterol (WMD −5.98%, 95% CI (−9.83, −2.13)), and VLDL cholesterol (WMD −14.18%, 95% CI (−19.03, −9.33)) and increased HDL cholesterol (WMD 7.13%, 95% CI (−9.83, −2.13)), with a lower risk of hypoglycemia defined as BS ≤ 70 mg/dL (RR 0.46, 95% CI (0.28, 0.75)). All doses of once-weekly tirzepatide (5 mg, 10 mg, and 15 mg) were superior or non-inferior to insulin. Once-weekly tirzepatide can be a substitution for long-acting insulin in type 2 diabetes with a greater efficacy.

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Fig. 2: The summary of efficacy outcomes.
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References

  1. GBD 2019 Diabetes in the Americas Collaborators. Burden of diabetes and hyperglycaemia in adults in the Americas, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Diabetes Endocrinol. 2022;10:655–67. https://doi.org/10.1016/S2213-8587(22)00186-3.

  2. Safiri S, Karamzad N, Kaufman JS, Bell AW, Nejadghaderi SA, Sullman MJM, et al. Prevalence, deaths and disability-adjusted-life-years (DALYs) due to type 2 diabetes and its attributable risk factors in 204 countries and territories, 1990-2019: results from the global burden of disease study 2019. Front Endocrinol. 2022;13:838027.

    Article  Google Scholar 

  3. Dahlén AD, Dashi G, Maslov I, Attwood MM, Jonsson J, Trukhan V, et al. Trends in antidiabetic drug discovery: FDA approved drugs, new drugs in clinical trials and global sales. Front Pharmacol. 2021;12:807548.

    Article  PubMed  Google Scholar 

  4. Gao L, Lee BW, Chawla M, Kim J, Huo L, Du L, et al. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial. Nat Med. 2023;29:1500–10.

    Article  CAS  PubMed  Google Scholar 

  5. Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet (Lond, Engl). 2021;398:583–98.

    Article  CAS  Google Scholar 

  6. Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with type 2 diabetes. Diab Care. 2023;46:998–1004.

    Article  CAS  Google Scholar 

  7. Seino Y, Fukushima M, Yabe D. GIP and GLP-1, the two incretin hormones: similarities and differences. J Diab Investig. 2010;1:8–23.

    Article  CAS  Google Scholar 

  8. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205–16.

    Article  CAS  PubMed  Google Scholar 

  9. Bhagavathula AS, Vidyasagar K, Tesfaye W. Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized phase II/III trials. Pharm (Basel, Switz). 2021;14:991.

    CAS  Google Scholar 

  10. Kiyosue A, Dunn JP, Cui X, Hickey A, Hirase T, Imaoka T, et al. Safety and efficacy analyses across age and body mass index subgroups in East Asian participants with type 2 diabetes in the phase 3 tirzepatide studies (SURPASS programme). Diab Obes Metab. 2023;25:1056–67.

    Article  CAS  Google Scholar 

  11. Gastaldelli A, Cusi K, Fernández Landó L, Bray R, Brouwers B, Rodríguez Á. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diab Endocrinol. 2022;10:393–406.

    Article  CAS  Google Scholar 

  12. Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet (Lond, Engl). 2021;398:143–55.

    Article  CAS  Google Scholar 

  13. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503–15.

    Article  PubMed  Google Scholar 

  14. Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022;327:534–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Inagaki N, Takeuchi M, Oura T, Imaoka T, Seino Y. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet Diab Endocrinol. 2022;10:623–33.

    Article  CAS  Google Scholar 

  16. Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet (Lond, Engl). 2023;402:613–26.

    Article  CAS  Google Scholar 

  17. Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet (Lond, Engl). 2021;398:1811–24.

    Article  Google Scholar 

  18. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg. 2021;88:105906.

    Article  PubMed  Google Scholar 

  19. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clin Res ed). 2019;366:l4898.

    Google Scholar 

  20. Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane database Syst Rev. 2019;10:Ed000142.

    PubMed  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.

    Article  PubMed  Google Scholar 

  23. Thomas MK, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K, et al. Dual GIP and GLP-1 receptor agonist tirzepatide improves beta-cell function and insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2021;106:388–96.

    Article  PubMed  Google Scholar 

  24. Kristensen FPB, Christensen DH, Callaghan BC, Stidsen JV, Nielsen JS, Højlund K, et al. The prevalence of polyneuropathy in type 2 diabetes subgroups based on HOMA2 Indices of β-cell function and insulin sensitivity. Diab Care. 2023;46:1546–55.

    Article  CAS  Google Scholar 

  25. Lingvay I, Cheng AY, Levine JA, Gomez-Valderas E, Allen SE, Ranta K, et al. Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: a post hoc analysis of the SURPASS-1 to −5 studies. Diab Obes Metab. 2023;25:965–74.

    Article  CAS  Google Scholar 

  26. Viljoen A, Pantalone KM, Galindo RJ, Cui X, Huh R, Hemmingway A, et al. Time to reach glycaemic and body weight loss thresholds with tirzepatide in patients with type 2 diabetes: a pre-planned exploratory analysis of SURPASS-2 and SURPASS-3. Diab Ther: Res Treat Educ Diab Relat Disord. 2023;14:925–36.

    Article  CAS  Google Scholar 

  27. Pedersen SD, Giorgino F, Umpierrez G, Thieu VT, Rodríguez A, Nicolay C, et al. Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: a post hoc assessment of the SURPASS clinical trial programme. Diab Obes Metab. 2023;25:2553–60.

    Article  CAS  Google Scholar 

  28. Wilson JM, Nikooienejad A, Robins DA, Roell WC, Riesmeyer JS, Haupt A, et al. The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diab Obes Metab. 2020;22:2451–9.

    Article  CAS  Google Scholar 

  29. Lingvay I, Mosenzon O, Brown K, Cui X, O’Neill C, Fernández Landó L, et al. Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from SURPASS clinical program. Cardiovascular Diabetol. 2023;22:66.

    Article  CAS  Google Scholar 

  30. Li S, Liu Z, Joseph P, Hu B, Yin L, Tse LA, et al. Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy. Eur Heart J. 2022;43:2852–63.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Moein Ala, Razieh Mohammad Jafari & Ahmad Reza Dehpour

  2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Moein Ala, Razieh Mohammad Jafari & Ahmad Reza Dehpour

  3. Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Poursalehian

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  1. Moein Ala
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  2. Razieh Mohammad Jafari
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Contributions

MA conceptualized this article, performed the literature search, reviewed the retrieved articles, analyzed data, wrote the draft, edited the draft, and designed the figures. MP performed the literature search, and reviewed the retrieved articles. RMJ and ARD critically edited the article. All authors had full access to data and approved the last version of this article for publication.

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Correspondence to Moein Ala.

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Ala, M., Mohammad Jafari, R., Dehpour, A.R. et al. Tirzepatide outcompetes long-acting insulin in managing type 2 diabetes: a meta-analysis of three phase 3 randomized controlled trials. Int J Obes 48, 1684–1695 (2024). https://doi.org/10.1038/s41366-024-01621-4

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